P833: CATEGORIZING HEMATOLOGICAL RESPONSE TO PEGCETACOPLAN IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A POST HOC ANALYSIS OF THE PHASE 3 PRINCE STUDY DATA
Authors: A. Risitano, R. Wong, M. Al-Adhami, J. Savage, R. Horneff, R. Peffault de Latour
Journal: HemaSphere (2022)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-mediated hematological disorder characterized by anemia, hemolysis, and bone marrow failure. Pegcetacoplan (PEG), an FDA/EMA-approved targeted C3 therapy for the treatment of PNH, can control intravascular and prevent extravascular hemolysis. A prior post hoc analysis of PEGASUS reported a higher proportion of patients presenting good or better hematologic responses to PEG versus eculizumab (Risitano A, et al., Blood, 2021;138 [Supplement 1]: 1104). The PRINCE study demonstrated efficacy/safety of PEG compared to control treatment (CTRL; supportive treatment of PNH without complement inhibitors) in complement-inhibitor naïve patients with PNH. Aims: This post hoc analysis categorized the hematologic response to PEG and CTRL at baseline and Week 26 in the PRINCE Trial (phase 3, multicenter, randomized, open-label, controlled trial [NCT04085601]). Methods: Adult complement-inhibitor naïve (no complement-inhibitor treatment within 3 months prior to screening) patients with PNH who had low hemoglobin (Hb) levels and high lactate dehydrogenase levels were included. Patients were randomized 2:1 to receive PEG or CTRL through Week 26. Hematologic response to PEG and CTRL was categorized as complete, good, partial, or minor at baseline and at Week 26 using the number of packed red blood cells transfusions needed in the last 6 months and Hb level at the specified timepoints (revised categorization criteria per Debureaux PE, et al. Bone Marrow Transplant. 2021; 56(10):2600-2602). Hematologic response categorization was performed according to the following criteria: Complete response: no transfusions, no anemia (≥12 g/dL); Good response: no transfusions, but with chronic mild anemia (10-12 g/dL); Partial response: no/occasional transfusions (≤2 units/6 months) and chronic moderate anemia (8-10 g/dL); Minor response: regular transfusions (≥3 units/6 months) and chronic moderate/severe anemia (<10 g/dL), or no/occasional transfusions (≤2 units/6 months) and chronic severe anemia (<8 g/dL). Any patients with missing data at Week 26 were evaluated using the most recent value within the 6 weeks prior. Statistical tests assessed significance for responses of ‘Good’ or ‘Complete’, collectively (Fisher’s Exact Test between PEG and CTRL groups at baseline; McNemar’s test within PEG group at baseline vs. Week 26). Results: In this study, 53 patients were randomized to PEG (n=35) or CTRL (n=18). At baseline, most patients had a partial or minor response to supportive therapy prior to randomization, with only 5.7% of patients in the PEG group and 0.0% in the CTRL group presenting a Good or Complete hematologic response (p= 0.5428). Hematologic response categorization for patients in the PEG group are shown for baseline and Week 26 (Figure). At Week 26, 80.0% of patients in the PEG group exhibited a Good or Complete response. The proportion of patients in the PEG group who demonstrated a Good or Complete response was significantly higher at Week 26 as compared to baseline (p<0.0001). One patient treated with PEG had missing data at Week 26 due to being lost to follow-up and was not evaluated. Image:Summary/Conclusion: This post hoc analysis of PRINCE trial data revealed that a substantial proportion of patients achieved good or complete hematologic response to PEG after 26 weeks. These findings further support the positive efficacy of PEG on hematologic parameters and provide evidence for the role of proximal complement inhibition on hematological and clinical improvements for patients with PNH.